title: Medium-sized FLT3 internal tandem duplications confer worse prognosis than short and long duplications in a non-elderly acute myeloid leukemia cohort.
abstract: Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 (FLT3) gene occur in about 25% of patients with adult acute myeloid leukemia (AML). The aim of our study was to investigate the frequency of FLT3-ITD mutations followed by a detailed analysis of the mutational load and size of ITD insertions in a cohort consisting of 324 patients younger than 60 years old and treated with curative intention. FLT3-ITD alone did not influence overall survival (OS) or disease-free survival (DFS). We observed worse OS and DFS for patients with high mutational load indicative for loss of the FLT3 wild type allele (p = 0.010, p = 0.038, respectively). In multivariate analyses, patients with FLT3-ITD(48-60bp) showed worse OS and DFS compared to other groups (FLT3-ITD(neg), FLT3-ITD (< 48b), FLT3-ITD (> 60bp); p = 0.014, p = 0.019, respectively). Our novel observation suggested that not only high FLT3-ITD load, but also medium-sized ITD insertions (48-60 bp) represented an adverse prognostic subgroup of patients with AML.
authors.affiliation: Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service , Budapest , Hungary.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Koszarska
authors.forename: Nora
authors.initials: N
authors.lastname: Meggyesi
authors.forename: Andras
authors.initials: A
authors.lastname: Bors
authors.forename: Arpad
authors.initials: A
authors.lastname: Batai
authors.forename: Otto
authors.initials: O
authors.lastname: Csacsovszki
authors.forename: Eniko
authors.initials: E
authors.lastname: Lehoczky
authors.forename: Emma
authors.initials: E
authors.lastname: Adam
authors.forename: Andras
authors.initials: A
authors.lastname: Kozma
authors.forename: Nora
authors.initials: N
authors.lastname: Lovas
authors.forename: Andrea
authors.initials: A
authors.lastname: Sipos
authors.forename: Tunde
authors.initials: T
authors.lastname: Krahling
authors.forename: Janos
authors.initials: J
authors.lastname: Dolgos
authors.forename: Peter
authors.initials: P
authors.lastname: Remenyi
authors.forename: Sandor
authors.initials: S
authors.lastname: Fekete
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Andrikovics
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D020080:Tandem Repeat Sequences; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia; FLT3 internal tandem duplication; molecular genetics; mutation